Background In a previous study we demonstrated that institution of biventricular pacing in chronic heart failure (CHF) acutely facilitates the arterial baroreflex. The arterial baroreflex has important prognostic value in CHF. We hypothesized that the acute response in baroreflex sensitivity (BRS) after institution of cardiac resynchronization therapy (CRT) has predictive value for mid-term response. Methods One day after implantation of a CRT device in 33 CHF patients (27 male / 6 female, age 66.5 ± 9.5 years, left ventricular ejection fraction 28 ± 7%) we measured noninvasive BRS and heart rate variability (HRV) in two conditions: CRT device switched-on and switched-off (on/off order randomized). Echocardiography was performed prior to implantation (baseline) and 6 months after implantation (follow-up). CRT responders were defined as patients in whom left ventricular end systolic volume (LVESV) at follow-up had decreased by 15%. Results Responders (69.7%) and non-responders (30.3%) had similar baseline characteristics. In responders, CRT increased BRS by 30% (P=0.03); this differed significantly (P=0.02) from the average BRS change (-2%) in the non-responders. Also, CRT increased HRV by 30% in responders (P=0.02), but there was no significant difference found compared to the increase in HRV (8%) in the non-responders. Receiver-operating characteristic (ROC) curve analysis revealed that the percetage BRS increase had predictive value for the discrimination of responders and non-responders (area-under-the-curve 0.69; 95% confidence interval 0.51-0.87; maximal accuracy 0.70). Conclusions Our study demonstrates that a CRT-induced acute BRS increase has predictive value for the echocardiographic response to CRT. This finding suggests that the autonomic nervous system is actively involved in CRT-related reverse remodelling.